Hemostasis analyzer and method

ABSTRACT

A method and device for blood hemostasis analysis is disclosed. A blood sample is displaced to reach a resonant state. The resonant frequency of the blood sample is determined before, during and after a hemostasis process. The changes in the resonant frequency of the blood sample are indicative of the hemostasis characteristics of the blood sample.

FIELD OF THE DISCLOSURE

[0001] This disclosure relates generally to blood analysis, and moreparticularly, to a blood hemostasis analyzer and method.

BACKGROUND

[0002] Blood is in liquid form when traveling undisturbed in bodilypassageways. However, an injury may cause rapid clotting of the blood atthe site of the injury to initially stop the bleeding, and thereafter,to help in the healing process. An accurate measurement of the abilityof a patient's blood to coagulate in a timely and effective fashion andto subsequent lysis is crucial to certain surgical and medicalprocedures. Also, accurate detection of abnormal hemostasis is ofparticular importance with respect to appropriate treatment to be givento patients suffering from clotting disorders.

[0003] Blood hemostasis is a result of highly complex biochemicalprocesses that transform the blood from a liquid state to a solid state.Characteristics of blood, such as strength of the clot, infer that themechanical properties of the blood are important in determiningcharacteristics rather than the viscosity of the blood when in a liquidstate.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004]FIG. 1 is a schematic diagram of a blood hemostasis analyzerconstructed in accordance with the teachings of the instant disclosure.

[0005]FIG. 2 is a graph representing hemostasis characteristics of ablood sample in accordance with the teachings of the instant disclosure.

[0006]FIG. 3 is a perspective and exploded sectional view of a containerfor holding a blood sample in accordance with the teachings of theinstant disclosure.

[0007]FIG. 4 is a schematic view of the container of FIG. 3 havingtherein a blood sample and vibrating the blood sample in accordance withthe teachings of the instant disclosure.

[0008]FIG. 5 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

[0009]FIG. 6 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

[0010]FIG. 7 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

[0011]FIG. 8 is a perspective view of a first exemplary stand for ablood hemostasis analyzer constructed in accordance with the teachingsof the instant disclosure.

[0012]FIG. 9 is a perspective view of a second exemplary stand for ablood hemostasis analyzer constructed in accordance with the teachingsof the instant disclosure.

DETAILED DESCRIPTION

[0013] Referring to FIG. 1, a blood hemostasis analyzer 10 in accordancewith the teachings of the instant disclosure is generally shown. Theanalyzer 10 operates under the principle that because hemostasis of ablood sample changes the blood sample from a liquid state to a gel-likestate, and the modulus of elasticity of the blood sample controls thenatural frequency of the blood sample, measuring the changes in thenatural frequency of the blood sample during hemostasis provides thehemostasis characteristics of the blood sample. In keeping with thisprinciple, the disclosed blood hemostasis analyzer 10 measures thechanges in the fundamental natural frequency of a blood sample duringhemostasis and lysis processes to provide hemostasis characteristics ofthe blood sample. To practice the foregoing principal, the analyzer 10generally includes a container 12 for holding a blood sample 14, ashaker 16 for displacing the container 12 to thereby excite the bloodsample 14 to a resonant vibration, and a sensor 18 for measuring theresulting amplitude of the blood sample 14.

[0014] An exemplary method by which the disclosed blood hemostasisanalysis is performed will now be described. Vibration of a liquid atresonance closely resembles sloshing, which is analogous to the motionof a pendulum. Accordingly, as blood transitions from a liquid state toa gel-like state and possibly to a solid state during clotting, thefundamental natural frequency of the blood increases. The disclosedexemplary method measures the changes in the fundamental naturalfrequency of the blood sample 14 during hemostasis/clotting and lysisprocesses.

[0015] Initially, a blood sample 14 is placed in the container 12. Thecontainer 12 is then vibrated by the shaker 16 so that the blood sample14, which is initially in a liquid state, is vibrating in a linearsloshing mode. A liquid typically vibrates near its first fundamentalnatural frequency in a sloshing mode, which can be defined as theswinging of the entire mass of the liquid in a container, hence theanalogy to a pendulum. The amplitude of the sloshing reaches maximumwhen the blood sample 14 is vibrated at its fundamental naturalfrequency. Thus, to initially excite the blood sample 14 to resonance,the shaker 16 vibrates the container 12 at or very near the fundamentalnatural frequency of the blood sample 14. Furthermore, the shaker 16vibrates the container 12 at or very near the fundamental naturalfrequency of the blood sample 14 as this frequency changes throughoutthe hemostasis and possibly lysis processes.

[0016] One of ordinary skill in the art will readily appreciate thenumerous methods by which the shaker 16 can vibrate the container 12 ator near the fundamental natural frequency of the blood sample 14throughout the hemostasis and lysis processes. However, in the disclosedexample, the container 12 is initially vibrated at a frequency below thefundamental natural frequency of the blood sample 14. The frequency isthen increased in small steps, and concurrently, the resultingdisplacement amplitudes of the blood sample 14 are measured. As thefrequency of vibration of the container 12 increases to near the bloodsample's fundamental natural frequency, the displacement amplitude ofthe blood sample 14 will dramatically increase. The displacementamplitude of the blood sample 14 will reach maximum at its fundamentalnatural frequency. Thus, monitoring the displacement amplitude of theblood sample 14 for a maximum provides a value for the fundamentalnatural frequency of the blood sample 14 when that maximum is reached.

[0017] As the hemostasis process continues, the foregoing method offinding the fundamental natural frequency of the blood sample 14 isrepeated. The measured fundamental natural frequencies of the bloodsample 14 when plotted vs. time result in a curve 30 similar to thatshown in FIG. 2. Curve 30 is typically represented with its mirror imagerelative to the x-axis, which is shown as curve 31. The shape of thecurve 30 is indicative of blood hemostasis characteristics. The x-axis32 represents time, while the y-axis 34 represents the fundamentalnatural frequency of the blood sample 14 during the hemostasis and lysisprocesses. One of ordinary skill in the art will appreciate that sincefrequency of the blood sample 14 is proportional to the modulus ofelasticity of the blood sample 14, the y-axis also represents thechanges in the modulus of elasticity of the blood sample 14 duringhemostasis and lysis processes.

[0018] One of ordinary skill in the art will readily appreciate that thesize of the frequency step by which the vibration frequency of thecontainer 12 is increased or decreased during testing will affect howquickly and efficiently the fundamental natural frequency of the bloodsample 14 is pinpointed. For instance, a very large frequency step maynot provide a detailed frequency resolution to locate a near accuratemeasure of the fundamental natural frequency of the blood sample 14. Onthe other hand, a very small frequency step may not provide a rapidapproach to pinpointing the fundamental natural frequency of the bloodsample 14. Accordingly, in order to find the fundamental naturalfrequency of the blood sample within the frequency range by which thecontainer 12 is vibrated, it may be necessary to search for thefundamental natural frequency of the blood sample 14 by changing thefrequency step and/or adding or subtracting the frequency step from thevibration frequency of the container 12 in a methodical manner. Numerousmathematical algorithms and methods are well known to those of ordinaryskill in the art, by which the frequency step can be methodically variedto provide a rapid pinpointing of a peak in amplitude of oscillation ofthe blood sample 14.

[0019] One of ordinary skill in the art can use other well known methodsfor finding the fundamental natural frequency of the blood samplethroughout the hemostasis and lysis processes. For example, displacingthe container 12 with a frequency function that emulates white noisehaving frequency components near or equal to the fundamental naturalfrequencies of the blood sample 14 throughout the hemostasis and lysisprocesses can excite the blood sample 14 to a resonant state. Whitenoise is a frequency function that includes frequency componentsselected within a range of frequencies. Because the blood sample willrespond with resonant excitation to a frequency that is equal or nearits fundamental natural frequency, a white noise having such a frequencycomponent will excite the blood sample 14 to a resonant state. One ofordinary skill in the art will readily appreciate that well knownmethods such as Fourier Frequency Analysis can be utilized to find thefundamental frequency of the blood sample 14 after being excited bywhite noise.

[0020] An exemplary device employing the foregoing method of determininghemostasis characteristics of a blood sample 14 will now be described.Referring to FIG. 1, the shaker 16 displaces the container 12 to excitethe blood sample 14 to resonant vibration. Generally, the shaker 16 is adevice capable of oscillating the container 12 with a desired frequencyand amplitude. One of ordinary skill in the art will appreciate thenumerous devices by which an object can be oscillated. In the disclosedexample, the shaker 16 is a dipcoil, which is similar to a voice coil ofa speaker. In other words, the shaker 16 includes an electromagnet thatoscillates relative to a stationary permanent magnet by having itscurrent driven by an electrical signal. The shaker 16 may be connectedeither directly or with a connecting link 36 to the container 12. Theconnecting link 36 transfers the motion created by the shaker 16 to thecontainer 12. As is well known to those of ordinary skill in the art,characteristics of the electrical signal, i.e., voltage, current,direction of current, etc., determine the characteristics of theoscillatory motion of the shaker 16. Accordingly, the shaker 16 candisplace the container 12 with any desired amplitude and frequencywithin the operational limits of the shaker 16.

[0021] The container 12 holds the blood sample 14 during the excitationof the blood sample 14. The container 12 may be any shape or size.However, the shape and size of the container may affect the operation ofthe analyzer 10, because the container 12 acts as a resonator. Thelarger the container 12, the lower the natural frequency of the bloodsample 14 will be. Furthermore, the container 12 cannot be too small sothat a meniscus effect is produced due to the surface tension in theblood sample 14. Conversely, if the container 12 is too large, a largeblood sample 14 will be needed for the analysis in the analyzer 10,which may not be medically acceptable.

[0022] An exemplary container 12 is shown in FIG. 3. The container 12has a lower portion 40 and an upper portion 42. The lower portion 40 andthe upper portion 42 are generally rectangular. The upper portion 42 hasa larger width, a larger length, and a smaller depth than the lowerportion 40, so as to provide an internal step 44. The container 12 alsoincludes a lid 46 that is sealably attached to the top of the uppersection 40. The container 12 includes a port 48 for receiving a bloodsample 14. To reduce the meniscus effect of the blood sample 14 whenplaced in the container 12, the lower portion 40 is filled with theblood sample up to where the upper portion 42 begins. Accordingly, thevolume of the blood sample 14 is substantially equal to the volume ofthe lower portion 40.

[0023] To prevent the blood sample 14 from evaporating during testingand to prevent contamination thereof, the port 48 may be self sealing.For example, the port 48 may be constructed from rubber or silicon sothat when a syringe needle is inserted therein, the rubber or siliconresiliently surrounds the syringe needle to substantially seal the portduring the injection of the blood sample 14 into the container 12. Whenthe needle is withdrawn from the port 48, resilience of the rubber orthe silicon substantially re-seals the hole created by the needle. Toprevent evaporation of the blood sample 14 and any reaction the bloodsample may have by being exposed to air, the container 12 can bepre-filled or pressurized with an inert gas, such as Helium.Alternately, the air in the container can be removed to provide a vacuuminside the container 12. One of ordinary skill in the art will recognizethat the pressure in the container 12 has minimal to no effect on thefundamental natural frequency of the blood sample 14. In the exampledisclosed herein, the container 12 is safely disposable and can besafely discarded after each use. The disposability of the container 12ensures that the blood sample 14 is safely handled during testing andsafely discarded after testing. In addition, the disposable container 12can be manufactured to be completely sealed and only provide accessthereto by the port 48. Thus, the disposability of the container 12,combined with the container 12 being completely sealed, ensure that theblood sample 14 is not exposed to air (i.e., to prevent the drying ofthe surface of the blood sample 14) or any other contaminants, andfurthermore, ensure safety in handling and disposing of the blood sample14 before, during, and after testing.

[0024] The analyzer 10 includes a slot (not shown) to receive thecontainer 12. One of ordinary skill in the art will readily appreciatethat the container 12 may be inserted in and removed from the slot inany manner desirable. However, to provide easy insertion and removal ofthe container 12 from the analyzer 10, the container 12 may include ahandle (not shown) that can be held by a user for insertion and removalof the container 12 to and from the analyzer 10, respectively.

[0025] To measure oscillations of the blood sample 14 as a result of thedisplacement of the container 12, a fixed electromagnetic source 60emits a beam 62 toward the blood sample 14. As shown in FIG. 1, thesource 60 may be part of the sensor 18 (i.e., an active sensor).Alternatively, the source 60 and a sensor 66 (i.e., a passive sensor)can be independent devices. The beam 62 is detected by the sensor 18after being reflected from the surface of the blood sample 14. Thecharacteristics of the beam after being reflected from the surface ofthe blood sample 14 are indicative of the movement of the blood sample14 in response to displacements of the container 12.

[0026] One of ordinary skill in the art will appreciate that theelectromagnetic beam of the source 60 may be produced by any emissionwithin the electromagnetic spectrum so long as the beam 62 can reflectfrom the surface of the blood sample 14, and the beam's characteristicsafter reflecting from the surface of the blood sample 14 indicate themovement of the blood sample 14.

[0027] In the disclosed example, the source 60 is a fixed LED (LightEmitting Diode) source that directs a beam 62 towards the blood sample14. The beam 62 is then reflected from the surface of the blood sample14. Accordingly, the container 12 has an optically transparent portionso that the beam 62 and its reflection 64 can enter and exit thecontainer 12, respectively. In the disclosed example, the lid 46 istransparent to light. One of ordinary skill in the art will recognizethat the lid 46, although transparent, will itself reflect some of thelight in the beam 62. To reduce the reflection of light from the lid 46,an anti-reflective coating may be applied to the lid 46. Suchanti-reflective coatings are well known to those of ordinary skill inthe art as they are applied to a variety of optical devices, such aseyeglasses, telescopes, cameras, etc. Although most liquids are highlytransparent to light, the surface of blood forms a highly reflectivesurface so that most of the beam 62 is reflected from the surface of theblood sample 14.

[0028] Referring to FIG. 4, the displacements of the blood sample 14relative to a rest position are shown with dashed lines 70 having anangle δ. Accordingly, the displacement of the blood sample 14 changesthe angle of the reflection 64 of the beam 62 by the same angle δ. Thesensor 18 intercepts the reflection 64 of the beam 62 from the surfaceof the blood sample 14 and produces an electric signal indicative of thedisplacement of the blood sample 14. In the disclosed example, thesensor. 18 includes a plurality of photo diodes that collectively detectthe displacement of the reflection of the beam 64. The outputs of thediodes are measured differentially so that peaks in the displacement ofthe blood sample 14, which are indicative of resonance, can beidentified.

[0029] In others example of the present disclosure, the vibrations inthe blood sample 14 may be measured by a number of other devices. In oneexample, acoustic sensors (not shown) disposed in the container 12 candifferentially measure the distance from the surface of the blood sample14 to the sensor, which is indicative of the vibration in the bloodsample 14. In another example, electrodes (not shown) arranged in thecontainer 12 function as either a capacitive or resistive bridge (i.e.,a Wheatstone bridge). The voltage differential of the capacitors or theresistors is indicative of the vibrations of the blood sample 14. In yetanother example, two photo diodes (not shown) can be placed on aninterior wall of the container near the surface of the blood sample 14.As the blood sample 14 vibrates, it partially or fully obscures one orboth of the diodes (i.e., preventing light from reaching the diodes).Accordingly, the outputs of the diodes are measured differentially sothat peaks in the displacement of the blood sample 14, which areindicative of resonance, can be identified

[0030] One of ordinary skill in the art will appreciate the numerousmethods and devices that can be used for driving the shaker 16 andanalyzing the signals from the sensor 18 for determining the hemostasischaracteristics of the blood sample 14. For instance, as shown in FIG.5, the blood hemostasis analyzer 10 can include an internal computingdevice 80 that includes the necessary hardware and software to drive theshaker 16 independently or in response to signals from the sensor 18.Furthermore, the internal computing device 80 can analyze the signalsfrom the sensor 18 to determine the fundamental natural frequencies ofthe blood sample 14 during hemostasis. As described in the foregoing,such an analysis will yield data for constructing the curves 30 andother data regarding the hemostasis characteristics of the blood sample14. In another example as shown in FIG. 6, the analyzer 10 can include amemory device 82 for storing the data from the sensor 18 for lateranalysis by an external computing device 84. The shaker 10 can be drivenby a predetermined method stored in the memory device 82, or by theexternal computing device 84. In yet another example shown in FIG. 7,the analyzer 10 does not include any internal memory or computingdevice. During testing, the analyzer 10 is in continuous and real-timecommunication with an external computing device 86 (e.g., laptop,personal digital assistant, desktop computer, etc.). The externalcomputing device 86 drives the shaker 16 and receives signals fromsensor 18 to determine the hemostasis characteristics of the bloodsample 14 as described in the foregoing. One of ordinary skill in theart will appreciate that numerous other well known methods, algorithmsand devices can be utilized to drive the shaker 16, independently or inresponse to signals from the sensor 18, and determine blood hemostasischaracteristics from the sensor signals. Furthermore, the determinedblood hemostasis characteristics can be conveyed to a user by a varietyof well known methods and devices, such as displaying data on a displayscreen, or printing the results on paper.

[0031] One of ordinary skill in the art will appreciate that theforegoing generalized device is very rugged and not easily susceptibleto damage from being mishandled. The disclosed device has a very smallnumber of moving parts or parts that are breakable. Furthermore, thesimplicity of the disclosed device provides for quick replacement of adefective part when necessary.

[0032] Ambient vibrations or seismic noise near the analyzer 10 candisturb or influence the blood hemostasis analysis. Accordingly, theanalyzer 10 can include a vibration filtering device onto which theanalyzer 10 is mounted. In a first example as shown in FIG. 8, thevibration filtering device is a hook 90, from which the analyzer 10 issuspended by a cable 92. In effect, the analyzer 10 is suspended fromthe hook 90 in a pendulum-like manner. Seismic noise or ambientvibration in a wide range of frequencies is dissipated through the hook90 and the cable 92 prior to reaching the analyzer 10. One of ordinaryskill in the art will appreciate that any wire that is connected to theanalyzer 10 for power or communication purposes can be carried by thecable 92 so as to not externally influence the motion of the analyzer 10(e.g., hanging wires contacting other objects). In a second example asshown in FIG. 9, the seismic filtering device is a platform 100 thatrests on a number of legs 102. In effect, the platform 100 is aninverted pendulum. In application, the analyzer 10 is placed on theplatform 100 so that any ambient vibration or seismic noise within awide frequency range is dissipated through the platform 100 prior toreaching the analyzer 10. One of ordinary skill in the art willappreciate many other ways of isolating noise, including use ofvibration absorbing foams, spring suspension and the like.

[0033] Although certain apparatus constructed in accordance with theteachings of the invention have been described herein, the scope ofcoverage of this patent is not limited thereto. On the contrary, thispatent covers all examples of the teachings of the invention fairlyfalling within the scope of the appended claims either literally orunder the doctrine of equivalents.

What is claimed is:
 1. An apparatus for measuring hemostasis comprising:a container adapted to hold a blood sample, the container including aportion transparent to an emission from a sensor; a shaker adapted todisplace the container in order to cause an excitation of the bloodsample, the blood sample being excited to a resonant state; and thesensor adapted to determine a movement of the blood sample within thecontainer responsive to the displacement of the container by the shakerby generating the emission and directing the emission toward the bloodsample through the portion; wherein data from the sensor is indicativeof the resonant state of the blood sample.
 2. An apparatus according toclaim 1, further comprising an analyzer coupled to the sensor to receivethe data from the sensor, the analyzer being adapted to derive ahemostasis characteristic of the blood sample based upon the data fromthe sensor.
 3. An apparatus according to claim 1, wherein the shakerdisplaces the container with a frequency function having randomlyselected frequency components selected from a range of frequencies. 4.An apparatus according to claim 1, wherein the shaker displaces thecontainer at a displacement frequency and varies the displacementfrequency responsive to changes in the resonant state of the bloodsample.
 5. An apparatus according to claim 1, wherein the containerincludes a self-sealing port for receiving the blood sample.
 6. Anapparatus according to claim 1, wherein the container is a sealedcontainer.
 7. An apparatus according to claim 1, wherein the containeris safely disposable.
 8. An apparatus according to claim 1, wherein thecontainer comprises a first portion connected to a larger secondportion, wherein the blood sample fills the first portion.
 9. Anapparatus according to claim 1, wherein the sensor is an optical sensor.10. An apparatus according to claim 1, wherein the sensor is an electricsensor.
 11. An apparatus according to claim 1, wherein the sensor is anacoustic sensor.
 12. An apparatus for measuring hemostasis comprising: aslot for receiving a container having therein a blood sample, whereinthe container includes a portion transparent to an emission from asensor; a shaker adapted to displace the container in order to cause anexcitation of the blood sample, the blood sample being excited to aresonant state; the sensor adapted to determine a movement of the bloodsample within the container responsive to the displacement of thecontainer by the shaker by generating the emission and directing theemission toward the blood sample through the portion; and an analyzercoupled to the sensor to receive data from the sensor, the analyzerbeing adapted to derive a hemostasis characteristic of the blood samplebased upon the data from the sensor; wherein the data from the sensor isindicative of the resonant state of the blood sample.
 13. An apparatusaccording to claim 9, wherein the shaker displaces the container with afrequency function having randomly selected frequency componentsselected from a range of frequencies.
 14. An apparatus according toclaim 9, wherein the shaker displaces the container at a displacementfrequency and varies the displacement frequency responsive to changes inthe resonant frequency of the blood sample.
 15. A method for measuringhemostasis comprising: providing a blood sample; exciting the bloodsample to a resonant state by displacing the blood sample to createmovement in the blood sample; observing the movement in the bloodsample; periodically determining a resonant frequency of the bloodsample to provide a plurality of resonant frequencies of the bloodsample; and deriving the hemostasis characteristics of the blood samplefrom the plurality of resonant frequencies of the blood sample.
 16. Amethod according to claim 15, further comprising displacing the bloodsample at a frequency, and incrementally varying the frequency until aresonant frequency of the blood sample is determined
 17. A methodaccording to claim 15, further comprising incrementally varying thefrequency from the resonant frequency to determine a plurality ofresonant frequencies of the blood sample before, during and afterhemostasis of the blood sample, wherein the plurality of the resonantfrequencies are indicative of the hemostasis characteristics of theblood sample.
 18. A method according to claim 15, further comprising:displacing the blood sample with a frequency function having randomlyselected frequency components selected from a range of frequencies; anddetermining a plurality of resonant frequencies of the blood samplebefore, during and after hemostasis of the blood sample; wherein theplurality of the resonant frequencies are indicative of the hemostasischaracteristics of the blood sample.
 19. A method for measuringhemostasis comprising: placing a blood sample in a container having aportion transparent to an emission from a sensor; displacing thecontainer with an shaker to cause movement in the blood sample;measuring the movement in the blood sample with a sensor receiving theemission indicative of the movement of the blood sample, wherein theemission contact at least a portion of the blood sample before beingreceived by the sensor; periodically determining a resonant frequency ofthe blood sample from the movement of the blood sample to provide aplurality of resonant frequencies of the blood sample; and deriving thehemostasis characteristics of the blood sample from the plurality ofresonant frequencies of the blood sample.
 20. A method according toclaim 19, further comprising: displacing the container at a frequency;incrementally varying the frequency until a resonant frequency of theblood sample is determined; and incrementally varying the frequency fromthe resonant frequency to determine a plurality of resonant frequenciesof the blood sample before, during and after hemostasis of the bloodsample; wherein the plurality of the resonant frequencies are indicativeof the hemostasis characteristics of the blood sample.
 21. A methodaccording to claim 19, further comprising: displacing the container witha frequency function having randomly selected frequency componentsselected from a range of frequencies; and determining a plurality ofresonant frequencies of the blood sample before, during and afterhemostasis of the blood sample; wherein the plurality of the resonantfrequencies are indicative of the hemostasis characteristics of theblood sample.
 22. A method according to claim 19, wherein placing theblood sample in the container further comprises injecting the blood intothe container through a self-sealing port on the container.
 23. Fortesting a blood sample, a sealed container for holding the blood samplecomprising: a wall defining an enclosed volume; a self-sealing one-wayport disposed on the wall and in communication with the enclosed volume;and a portion of the wall being transparent to a sensor emission; andwherein the port is adapted to allow insertion of the blood sample intothe container and to retain the sample within the volume during testingof the sample.
 24. A container according to claim 23, the enclosedvolume comprising a first portion connected to a larger second portion,wherein the blood sample fills the first portion.
 25. A containeraccording to claim 23 adapted to be safely disposable.